title: Cholinergic drugs inhibit in vitro megakaryopoiesis via the alpha7-nicotinic acetylcholine receptor.
abstract: Besides thrombopoietin several additional factors (i.e neurotransmitters and receptors) are known to be involved in the regulation of megakaryopoiesis at different stages. Recently, we identified functional α7 nicotinic acetylcholine receptors (nAChRα7) on platelets and megakaryocytic precursors. In platelets nAChRα7 form functional Ca(2+) channels and are involved in fibrinogen receptor activation and aggregation. Here, we investigated the impact of nAChRα7 on the differentiation of the human megakaryoblastic cell line MEG-01. In vitro differentiation of MEG-01 cells was induced by the phorbol ester TPA for 5 days in the absence or presence of nicotine or the nAChRα7-selective antagonist methyllycaconitine (MLA), and this was monitored by the expression of the megakaryocytic antigens CD41 and CD61. In the presence of the cholinergic drugs (nicotine or MLA) CD41 and CD61 expression was significantly reduced, both at RNA and protein level. We postulate that the nAChRα7 receptor is involved in megakaryopoietic signal transduction and gene regulation. This could affect the generation of platelets in vivo and contribute to the development of novel therapeutic drugs that regulate platelet formation.
authors.affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg - Hessen, Mannheim, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Thornton
authors.forename: Angelika
authors.initials: A
authors.lastname: Schedel
authors.forename: Sabrina
authors.initials: S
authors.lastname: Besenfelder
authors.forename: Harald
authors.initials: H
authors.lastname: Klüter
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D018678:Cholinergic Agents / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D039661:Integrin beta3 / Q000096:biosynthesis / Q000235:genetics; D055016:Megakaryocyte Progenitor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D040201:Platelet Membrane Glycoprotein IIb / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D034061:Thrombopoiesis / Q000187:drug effects*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D018678:Cholinergic Agents; C579167:Chrna7 protein, human; C061248:ITGB3 protein, human; D039661:Integrin beta3; D018733:Nicotinic Antagonists; D010703:Phorbol Esters; D040201:Platelet Membrane Glycoprotein IIb; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D009538:Nicotine; D000157:Aconitine